Histone acetylation/deacetylation controls chromatin activity and subsequent gene transcription. Recent studies demonstrated the activation of histone deacetylases (HDACs) in various human malignancies, however, the expression and function of HDACs in ovarian tumors are not fully understood. In this study, we examined the immunohistochemical expression of HDAC1, HDAC2 and HDAC3 using tissues obtained from 115 cases of ovarian tumors and compared it with that of Ki-67 (a growth marker), p21, and E-cadherin and clinicopathological parameters. In addition, we analyzed the effect of specific siRNA for HDAC1, HDAC2 and HDAC3 on the expression of cell cycle-related molecules and E-cadherin to clarify the functional difference among the three HDACs. The results indicated that the immunohistochemical expression of nuclear HDAC1, HDAC2 and HDAC3 proteins increased stepwise in benign, borderline and malignant tumors. The expression of HDAC1 and HDAC2 was correlated with Ki-67 expression and that of HDAC3 was inversely correlated with E-cadherin expression. Among the HDACs examined, only HDAC1 was associated with a poor outcome, when overexpressed. Treatment with HDAC inhibitors suppressed the proliferation of ovarian cancer cells in association with apoptosis. A specific siRNA for HDAC1 significantly reduced the proliferation of ovarian carcinoma cells via down-regulation of cyclin A expression, but siRNA for HDAC3 reduced the cell migration with elevated E-cadherin expression. Our results suggested that HDAC1 plays an important role in the proliferation of ovarian cancer cells, whereas HDAC3 functions in cell adhesion and migration. Therefore, specific therapeutic approaches should be considered according to the HDAC subtypes.(c) 2010 UICC.

We have performed the clinical evaluations of preoperative induction chemoradiotherapy (CRTx) for 25 patients with non small-cell lung cancer (male: 19, female: 6, mean age: 66.4-year-old). The clinical stages of these patients were IIA: 1, IIB: 7, IIIA: 14, and IIIB: 3, respectively. In the histological type of lung cancer, there were 12 patients of adenocarcinoma, 7 of squamous cell carcinoma, 1 of adenosquamous carcinoma, 1 of anaplastic carcinoma, and 4 of large cell carcinoma. We applied two courses of regimen as the pre-operative chemotherapy (CDDP+DOC or CBDCA+PTX). Twenty-four patients received radiotherapy as the concurrent radiotherapy (44 Gy: 22 patients, 60 Gy: 2 patients). Among the 25 patients, 16 patients accomplished both chemotherapies, and the effects of the treatment were as follows: CR; none, PR; 15, SD; 9, respectively. And the other patient was not an evaluable case due to atelectasis. Histopathological effects (Ef) were Ef-3: 3, Ef-2: 11, Ef-1: 7, Ef-0: 1 and Ef was not evaluable in 3 cases. Post operative pathological findings showed that 14 patients were down staged. There were no operative mortality associated with the operation, and no serious morbidity case was observed. Eighteen patients were survived and 1 patient was survived with tumor metastases. Only one patient died of recurrence in the upper mediastinal lymph nodes, 3 patients died of the brain metastases, one died of hepatic metastasis, and one died of cryptogenic sudden death. As a result, there was no serious operative morbidity observed in the course of this CRTx. We therefore recommend that induction chemoradiotherapy as a beneficial pre-operative treatment.

Minimally invasive thymectomy procedures have been proposed for nonthymomatous myasthenia gravis. However, few reports stressed that the lower invasiveness or cosmetic benefits also evaluated the rationale of a thymectomy, which is performed to remove as much thymic tissue as possible. We retrospectively reviewed 30 consecutive patients who underwent a bilateral video-assisted thoracoscopic extended thymectomy (VATET) and compared the results with those of 26 patients who underwent a transsternal extended thymectomy (TSET) to determine the amount of removed thymic tissue and clinical prognosis. The amount of blood loss during the operation for VATET (median 60 mL; range nearly 0 to 940 mL) was significantly lower as compared with that of TSET. The median weight of removed thymic tissue (37.0 g; 18.3 to 100.0 g) and remission rates (1 y: 12.5%; 3 y: 30.8%; 4 y: 44.4%) of VATET were comparable with those of TSET. The VATET group had a similar amount of thymo-fatty tissue removed and feasible clinical outcomes as compared with the TSET group, indicating that VATET provides a proper balance between less invasiveness and radical capability.

We investigated the mechanisms of thermosensitization related to combination therapy with sesquiterpene lactone parthenolide (PTL), a nuclear factor-kappaB (NF-kappaB) inhibitor, and hyperthermia using human lung adenocarcinoma cells A549. The kinetics of apoptosis induction and cell cycle of cells treated with PTL, heating, and combined treatment were examined by flow cytometric analysis. The flow cytometric distribution was calculated and expressed as a percentage. The ratios of the sub-G1 division, used to determine the induction of apoptosis, increased significantly with the combination therapy. Furthermore, the ratios of G2/M division increased and the ratios of G0/G1 division decreased, indicating cell cycle arrest in G2/M. The cell phase response to PTL by A549 cells synchronized in the G1/S border with hydroxyurea was also analyzed. PTL showed remarkable cytotoxicity at the S phase of the cell cycle in A549 cells at all concentrations as well as with hyperthermia, thus PTL reduced the number of cells in the proliferation phase. Inhibition of intracellular transcription factor NF-kappaB activation in A549 cells with various incubation periods after treatments with PTL, heating and combined treatment was examined by Western blot analysis. Unexpectedly, PTL alone did not inhibit NF-kappaB activation in cells stimulated with TNF-alpha, while heating alone inhibited NF-kappaB early after treatment and that effect faded over time. In contrast, PTL combined with heating completely inhibited NF-kappaB activation. Our results demonstrated that PTL and heating in combination cause significant thermosensitization of A549 cells via induction of apoptosis or cell cycle arrest in G2/M by inhibiting NF-kappaB activation in a synergistic manner.

OBJECTIVES:: The purpose of this study was to examine CD44v6 expression in intraductal papillary mucinous neoplasms (IPMNs) and clarify the role of CD44v6 in progression, invasion, metastasis, and morphogenesis of IPMNs. METHODS:: One hundred fifty-one samples of IPMNs and 30 normal controls were subjected to immunohistochemical analysis for CD44v6. The IPMNs were divided into 4 groups according to the grade of atypia (adenoma, borderline IPMN, noninvasive carcinoma, and invasive carcinoma) and 5 subtypes according to histological phenotype (gastric, intestinal, pancreatobiliary, oncocytic, and unclassified). Correlations were investigated between CD44v6 expression and clinicopathological characteristics including grade of atypia, subtype, lymph node metastasis, and invasion pattern. RESULTS:: Whereas normal ductal epithelium did not express CD44v6, CD44v6 expression was observed from the early stage of IPMNs and up-regulated in the progression of IPMNs to invasive carcinoma. CD44v6 expression in intestinal-type IPMNs was significantly lower compared with that in other subtypes. Whereas no correlation was observed between lymph node metastasis and CD44v6 expression in invasive IPM carcinomas, the invasion pattern was significantly correlated to CD44v6 expression. CONCLUSIONS:: The present data indicate that CD44v6 expression determines the morphology and aggressiveness of IPMNs and is involved in development and invasion of IPMNs.

PURPOSE: We evaluated the long-term pulmonary function after lobectomy for congenital cystic lung disease, in both infants and children, using radionuclide imaging (RI). METHODS: We performed a retrospective review of 93 patients who underwent resection of cystic lung lesions between 1974 and 2001. The results of postoperative lung volume/perfusion scintigraphy at 1 (n = 64), 5 (n = 32), and 10 years (n = 18) after surgery (V1, 5, 10/Q1, 5, 10) and mean transit time (MTT-a marker for air-trapping) at 1, 5, and 10 years after surgery (MTT1, 5, 10) were compared with respect to age at operation, preoperative infection, underlying disease, and type of surgery. RESULTS: Patients who were younger than 1 year at the time of surgery showed a significantly lower MTT5 (1.09 +/- 0.08) and MTT10 (1.15 +/- 0.11) than patients who were older than 1 year at the time of surgery (MTT5, 1.49 +/- 0.67; MTT10, 1.54 +/- 0.33). The noninfected group had significantly higher Q10 and lower MTT10 values (P <.05) compared to the infected group. No significant differences were observed between patients with single lobe vs multiple lobe resection. CONCLUSIONS: The optimal age for surgery in patients with congenital cystic lung disease appears to be less than 1 year.

The patient was a 36-year-old male. He visited our department in February 2004 as a prior chest X-ray revealed multiple nodular shadows. After further examinations, he was diagnosed with stage IV adenocarcinoma of the lung. As treatment, 5 courses of carboplatin (CBDCA)+docetaxel (DOC), 3 courses of CBDCA+gemcitabine (GEM), 6 weeks of gefitinib, and 3 courses of GEM were administered. However, the tumor progressed, and S-1 (120 mg/day, 2 weeks on, 1 week off) was administered as the sixth regimen from May 2006. No severe side effects were observed, and an antitumor action was achieved over a relatively long period. Therefore, it was suggested that a single administration of S-1 for non-small cell lung cancer, which had been treated with other multiple regimens, is safe, and long-term control of the disease can be expected.

Thymoma is a thymic epithelial neoplasm which induces T cell development. However, the frequency of mature CD4(+) T cells in thymomas is lower than in normal thymi. Recently, CD4/CD8 lineage commitment has been elucidated in animal model. The zinc finger transcription factor Th-POK is a critical factor to CD4(+) T cell development in CD4/CD8 lineage commitment, whereas CD8(+) T cell development requires the transcription factor Runx3. These factors antagonize in CD4/CD8 lineage commitment. In this study, we examined Th-POK and Runx3 mRNA expression in the T cell subsets of human normal thymus and thymoma. A quantitative reverse transcriptase-polymerase chain reaction examination revealed that Th-POK expression in normal thymi was higher in the CD4(+)CD8(-) subset than in the CD4(+)CD8(+) and CD4(-)CD8(+) subsets. In thymomas, Th-POK expression in the CD4(+)CD8(-) subset was significantly lower than that in normal thymi, and was significantly correlated with the proportion of CD3(+) cells in the CD4(+)CD8(-) subset. However, Th-POK expressions of the CD3(+)CD4(+)CD8(+) and CD3(+)CD4(+)CD8(-) subsets were not impaired in thymomas compared to normal thymi. These results suggest that thymoma neoplastic epithelial cells can induce Th-POK expression similarly to the normal thymic epithelial cells. In addition, there was no significant difference in Runx3 expression between normal thymi and thymomas. Therefore, CD4/CD8 lineage commitment dependent on Th-POK and Runx3 system seems to be working even in the neoplastic environment formed by human thymomas.

Slide tracheoplasty has become a standard procedure to treat long-segment congenital tracheal stenosis because it is a reasonable and simple technique. Slide tracheoplasty does not affect the carina during long-segment congenital tracheal stenosis management, and thus lesions of the carina, such as stenosis and tracheobronchomalacia can become important causes of extubation failure after surgery. In this manusript, we describe the effectiveness of our modified slide tracheoplasty, which includes reconstruction of the carina. We have performed this technique on three patients, all of whom were extubated without developing any respiratory symptoms.

It has been stated that postpartum endometritis in dairy cows has a tendency to cure without intervention. The objectives of this field study, therefore, were to determine the proportions of cows with spontaneous clinical recovery or persistence of postpartum endometritis and to determine some risk factors for its persistency in dairy cows (Bos taurus). Holstein-Friesian cows (n=441 lactations) from seven dairy herds were examined monthly by vaginoscopy and transrectal palpation. A cow was considered to have "postpartum endometritis" if it had pus in the cervico-vaginal discharge at the first postpartum examination during Days 15 to 60 (Day 0=day of calving); this was classified as mild, mucopurulent, or purulent endometritis, or endometritis with fluid in uterus. Furthermore, a cow with evidence of endometritis at least once during Days 61 to 150 was considered to have "persistence (or recurrence) of endometritis." A total of 104 (23.6%) lactations had postpartum endometritis, of which 25.3% had persistence or recurrence of clinical endometritis. Cows with persistence or recurrence of endometritis became pregnant at a slower rate (hazard ratio [HR]=0.28; P<0.001) than those with no endometritis until Day 150. Calving in summer (odds ratio [OR]=7.00; P=0.04), early postpartum complications (OR=6.58; P=0.05), moderate (OR=4.03; P=0.08) and severe (OR=30.99; P=004) degrees of urovagina, and mucopurulent (OR=9.54; P=0.02) and purulent (OR=5.70; P=0.04) endometritis were risk factors for the persistence or recurrence of endometritis. Furthermore, 10.6% of cows that had not shown signs of postpartum endometritis had a new diagnosis of endometritis during Days 61 to 150. Some risk factors for the new diagnosis of endometritis beyond Day 60 were early postpartum complications (OR=2.82; P=0.03) and moderate (OR=5.00; P=0.001) or severe (OR=12.63; P<0.001) degrees of urovagina. In conclusion, approximately one quarter of cows with postpartum endometritis had persistence of endometritis until or beyond the breeding period. Risk factors for the persistence of clinical endometritis were summer calving, early postpartum complications, clinically relevant urovagina, and clinically relevant endometritis within 2 mo postpartum.